Ferric Carboxymaltose to Improve Skeletal Muscle Metabolism in Heart Failure Patients With Functional Iron Deficiency

Phase 2TerminatedNCT03218384

NYU Langone Health20 enrolled

Overview

The purpose of this study is to better understand how body levels of iron affect the ability to exercise in patients with heart failure (HF). Heart failure is a condition in which abnormal pumping action of the heart reduces the flow of blood to the body. Patients with heart failure may feel shortness of breath or leg fatigue when they exercise. Iron is an essential nutrient in the diet. In heart failure patients, low body levels of iron might increase shortness of breath and fatigue.

The purpose of this prospective, double blind parallel group randomized study is to compare the effects of ferric carboxymaltose vs. placebo on skeletal muscle mitochondrial oxidative capacity, submaximal exercise tolerance, and health-related quality of life in non-anemic Heart Failure (HF) patients with functional iron deficiency.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Iron-deficiency

Interventions

Ferric CarboxymaltoseDRUG

Intravenous Ferric Carboxymaltose 750 mg mixed under sterile conditions in 100 ml of normal saline for final concentration of 7.5 mg/ml and administered via volumetric infusion pump over 15 minutes.

PlaceboDRUG

100 ml of normal saline solution, and administered via volumetric infusion pump over 15 minutes.

31P MRS/MRIDEVICE

Each participant will perform the same rhythmic plantar extension exercise protocol twice, for sequential acquisition of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) measurements. For the exercise protocol, the participant will lay supine on the scanning table with the right leg inside the volume coil. The exercise consists of repeated plantar flexion movements using resistance bands at a frequency of one repetition per second for 1-2 minutes. Data are collected continuously for 2 minutes before the exercise (baseline), during exercise, and 5 minutes after the exercise for the MRS and MRI experiments.

Eligibility

Sex: ALLMin age: 21 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Symptomatic NYHA Class II-III heart failure \>3 months * Guideline-recommended heart failure treatment for \> 3 months * Hemoglobin \>13 g/dl for men and \>12 g/dl for women * Functional iron deficiency (defined as serum ferritin level \<100 ng/ml or between 100 and 299 ng/ml with transferrin saturation \<20%) * Left ventricular ejection fraction \<40%, or left ventricular ejection fraction ≥40% with left atrial enlargement (left atrial volume index \>28 ml/m2) and/or left ventricular hypertrophy (left ventricular mass index \>95 g/m2 (women) or \>115 g/m2 (men) determined by echocardiogram within last 24 months. * Able and willing to provide written informed consent Exclusion Criteria: * Presence of implantable defibrillator, permanent pacemaker, other metal implant not compatible with 3TMRS/MRI, or other contraindication to 3T MRS/MRI procedures * Heart failure due to infiltrative cardiomyopathy, restrictive cardiomyopathy, or hypertrophic cardiomyopathy * Weight \<50 kg or \>120 kg * Coronary or cerebral atherothrombotic events in the past 6 months * Hospitalization of emergency room visit for heart failure within past 3 months * ICD shock in last 3 months * Known peripheral artery disease or ankle-brachial index \<0.9 at screening visit * Exercise primarily limited by angina, lung disease or neuromuscular disease * Systolic blood pressure \<100 or \>160 mmHg * Heart rate \<50 or \>110 min-1 * Estimated glomerular filtration rate \<30 ml/min * Liver function tests \>3 times upper limit of normal * Serum phosphate below normal limit * Pregnant or breast-feeding women * Women of child-bearing potential unwilling to use recommended contraception methods during the study * Treatment with oral iron supplements (except multivitamins) in past year * Treatment with intravenous iron in past year * Treatment with erythropoiesis stimulating agents in the past year * Known intolerance of intravenous iron * History of anaphylaxis * Participation in another clinical trial within last 30 days.

Locations (1)

New York University School of Medicine

New York, New York, United States

Outcomes

Primary Outcomes

Change From Baseline in Post-Exercise Phosphocreatine Recovery Time

Post-exercise phosphocreatine recovery time (in seconds) will be used to assess mitochondrial oxidative capacity. It is measured non-invasively with 31P-magnetic resonance spectroscopy.

Time frame: Baseline, Week 4

Secondary Outcomes

Change From Baseline in 6-Minute Walk Test Distance

The 6-minute walk test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes.

Time frame: Baseline, Week 4

Change From Baseline in Kansas City Cardiomyopathy Questionnaire Score

23-item self-assessment of symptoms, physical and social limitations, and quality of life in patients with heart failure. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best. The total score ranges from 0-100, with higher scores indicating better health status. An increase in scores indicates health status improved during the observational period.

Time frame: Baseline, Week 4

Change From Baseline in Hemoglobin Levels

Hemoglobin is a protein in red blood cells that carries oxygen. Hemoglobin levels (g/dL) were measured in laboratory analyses using patient blood samples.

Time frame: Baseline, Week 4

Change From Baseline in Serum Ferritin Levels

Ferritin is a blood protein that contains iron. Serum ferritin levels (ng/ml) were measured in laboratory analyses using patient blood samples.

Time frame: Baseline, Week 4

Change From Baseline in Transferrin Saturation

Transferrin saturation, measured as a percentage, is the value of serum iron divided by the total iron-binding capacity of the available transferrin. Transferrin saturation was measured in laboratory analyses using patient blood samples.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.